A novel uracil-DNA glycosylase family related to the helix-hairpin-helix DNA glycosylase superfamily

Nucleic Acids Res. 2003 Apr 15;31(8):2045-55. doi: 10.1093/nar/gkg319.

Abstract

Cytosine bases can be deaminated spontaneously to uracil, causing DNA damage. Uracil-DNA glycosylase (UDG), a ubiquitous uracil-excising enzyme found in bacteria and eukaryotes, is one of the enzymes that repair this kind of DNA damage. To date, no UDG-coding gene has been identified in Methanococcus jannaschii, although its entire genome was deciphered. Here, we have identified and characterized a novel UDG from M.jannaschii designated as MjUDG. It efficiently removed uracil from both single- and double-stranded DNA. MjUDG also catalyzes the excision of 8-oxoguanine from DNA. MjUDG has a helix-hairpin-helix motif and a [4Fe-4S]-binding cluster that is considered to be important for the DNA binding and catalytic activity. Although MjUDG shares these features with other structural families such as endonuclease III and mismatch-specific DNA glycosylase (MIG), unique conserved amino acids and substrate specificity distinguish MjUDG from other families. Also, a homologous member of MjUDG was identified in Aquifex aeolicus. We report that MjUDG belongs to a novel UDG family that has not been described to date.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Archaeal Proteins / genetics
  • Archaeal Proteins / isolation & purification
  • Archaeal Proteins / metabolism
  • DNA Glycosylases*
  • DNA Repair
  • Escherichia coli / genetics
  • Guanosine / analogs & derivatives*
  • Guanosine / metabolism
  • Methanococcus / enzymology
  • Methanococcus / genetics
  • Molecular Sequence Data
  • N-Glycosyl Hydrolases / genetics
  • N-Glycosyl Hydrolases / isolation & purification
  • N-Glycosyl Hydrolases / metabolism*
  • Oligonucleotides / metabolism
  • Phylogeny
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Uracil-DNA Glycosidase

Substances

  • Archaeal Proteins
  • Oligonucleotides
  • Recombinant Proteins
  • Guanosine
  • 8-hydroxyguanosine
  • DNA Glycosylases
  • N-Glycosyl Hydrolases
  • Uracil-DNA Glycosidase
  • DNA-3-methyladenine glycosidase II